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TLR2 is Required for the Altered Transcription of p75NGF Receptors in Gram Positive Infection

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Abstract

Neuroimmune interactions play a decisive role in neuronal cell survival and cell death during neuronal injury, oxidative and free radical stress. In neurons, NGF occupancy of p75 neurotrophin receptor (p75NTR) has been shown to promote neuronal apoptosis, while occupancy of tropomyosin receptor kinase A (TrkA) promotes survival of injured neurons. In macrophages, recent results suggest that NGF via TrkA mediates resistance to cell death through the interaction with TLR2. We have investigated the transcriptional regulation of TrkA, p75NTR and their ligand nerve growth factor β (NGFβ) upon stimulation with the TLR2 ligand Staphylococcus aureus in the spleen of C57BL/6 mice, TLR2 (−/−) and p75NTR (−/−) mice. S. aureus challenge (i.p.) resulted in a significant increase in NGFβ mRNA levels in C57BL/6 (100%), TLR2 (−/−) (300%) and p75NTR (−/−) mice (355%). TrkA mRNA levels were upregulated only in p75NTR (−/−) mice (87%) whereas in TLR2 (−/−) mice they remained unchanged and even decreased in C57BL/6 mice (46%). p75NTR mRNA was increased in spleen of C57BL/6 mice (60%) whereas the levels in TLR2 (−/−) mice remained almost unchanged. Finally, TLR2 mRNA was upregulated by 350% in C57BL/6 mice and by 283% in p75NTR (−/−) mice. These data suggest that in splenocytes signaling via TLR2 is required for Gram positive infection mediated alteration of neurotrophin receptor expression as observed in an in vivo infection model with transgenic mice. This observation provides a link between Gram-positive infection and neurotrophic responses, which may be important in preserving neurons at sites of the infection.

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Abbreviations

TLR2 :

toll-like receptor 2

p75NTR :

p75 neurotrophin receptor

TrkA :

tropomyosin receptor kinase A

NGFβ :

nerve growth factor β

PCR :

polymerase chain reaction

SA :

Staphylococcus aureus

CFU :

colony-forming units

PBS :

phosphate-buffered saline

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Acknowledgements

The Dana Foundation grant (to RJU and TB), Fellowship of the Swiss National Science Foundation (to SW). The authors would like to thank Dr. John Mathison for providing a clinical isolate of Staphylococcus aureus. This article is manuscript no. 17222-NP from The Scripps Research Institute.

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Authors and Affiliations

  1. The Harold L. Dorris Neurological Research Center, Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA

    Sebastian A. Wirz & Tamas Bartfai

  2. Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA

    Peter S. Tobias & Richard J. Ulevitch

  3. Institut Pasteur INSERM CR1,25,28 rue du Docteur Roux, Paris Cedex 15, 75724, France

    Laurence Aribibe

  4. The Harold L. Dorris Neurological Research Center, Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA

    Tamas Bartfai

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  1. Sebastian A. Wirz
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  2. Peter S. Tobias
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  3. Richard J. Ulevitch
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  4. Laurence Aribibe
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  5. Tamas Bartfai
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Correspondence to Tamas Bartfai.

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Special Issue Dedicated to Miklós Palkovits.

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Wirz, S.A., Tobias, P.S., Ulevitch, R.J. et al. TLR2 is Required for the Altered Transcription of p75NGF Receptors in Gram Positive Infection. Neurochem Res 31, 297–301 (2006). https://doi.org/10.1007/s11064-005-9020-8

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  • DOI: https://doi.org/10.1007/s11064-005-9020-8

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